IMPAIRMENTS AND BONE REMODELING IN AGING PAGETS PATIENTS

老年 PAGETS 患者的损伤和骨重塑

• 批准号: 6112761
• 负责人: KENNETH W. LYLES
• 金额: $ 4.09万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6112761
• 关键词: aging; alkaline phosphatase; chordate locomotion; clinical research; clinical trials; functional ability; gait; human old age (65+); human subject; human therapy evaluation; hydroxyproline; osteitis deformans; pain; physiologic bone resorption; placebos; skeletal disorder chemotherapy; social behavior; urinalysis

Purpose: The purpose of this study is to determine if pamidroante will improve mobility impairments, functional status, pain, and psychosocial performance in patients with Paget's disease of bone. Methods: In order to determine if pamidronate will improve mobility impairments, functional status, pain, and psychosocial performance, we propose to use a randomized, double-blind, placebo-controlled trial in which 66 patients with active Paget's disease of femur, tibia, and/or acetabular portion of the ilium will be treated (pamidronate or placebo) and then followed for 6 months. All patients who enter the trial must have documented impairments in mobility, defined as an abnormal mobility measure (ten foot walk time, 360 degree turn, mobility skills protocol score, or 6 minute walk distance) and bone resorption or formation markers that are at least twice the normal level. When patients who have Paget's disease enter the study, they will have baseline measures performed and then be randomized to receive pamidronate 90mg intravenously over six hours or placebo. Measurements will be made at one, three and six months post therapy. Changes in mobility impairments will be assessed by measuring changes in ten foot walk time, (primary response variable), mobility skills protocol score, steps to make a 360 degree turn, or six minute walk distance. Changes in functional status impairments will be assessed with the Functional Status Questionnaire (FSQ). The primary response variable for functional status will be the instrumental activities of daily living scale of the FSQ. Changes in pain will be assessed by the West Haven Pain Inventory. Changes in impairments in psychosocial performance will be measured with the Rosenberg Self-Esteem Scale, the Beck Depression Scale and the Hopkins Symptom Checklist 90 Revised. Changes in bone remodeling activity will be followed by measuring serum alkaline phosphatase levels and urinary hydroxyproline and N-Telepeptide excretion. Results: Patients continue to be actively recruited and enrolled in this trial. Over the past year on the GCRC twenty-six patients were evaluated who were potential candidates for the study. Of the twenty-six, six were enrolled and two more have been offered a chance to participate in the study but have not yet been consented. We have treated the six patients with pamidronate, a second generation bisphosphonate, and shown improvement in mobility and functional status impairments as well as bone remodeling activity. Significance: Paget's disease of bone is a chronic skeletal disease that affects elderly people and is characterized by areas of increased skeletal remodeling which can lead to pain, deformity, secondary arthritis, fractures and rarely malignant degeneration. Several studies suggest that Paget's disease affects 1.8-5% of people over 60 years of age and 10% of people at 90 years of age. Improved therapy will enhance the ability of these patients to function in normal life activities. Future plans: Since the trial was started, two new bisphosphonates have been approved by the FDA to treat Paget's disease of bone: Alendronate (Fosamax) and Risedronate (Actonel). Both of these drugs are oral preparations and some patients have wished to receive oral medication rather than an intravenous preparation. More importantly, these drugs give many patients sustained biochemical and clinical remissions of their Paget's disease lasting 24 to 36 months. This means that many of the patients referred for evaluation of their Paget's disease do not need treatment of their disease as frequently as we had initially planned for this study.

目的：这项研究的目的是确定Pamidroante是否会改善Paget骨骼疾病患者的迁移率障碍，功能状况，疼痛和社会心理表现。方法：为了确定副膦酸盐是否会改善动机障碍，功能状态，疼痛和社会心理表现，我们建议使用一项随机的，双盲的，安慰剂对照的试验，其中有66例活跃的股骨，tibia，tibia和/或iLium的腹部分配的患者会被治疗（然后是pamidrate and the pamidronate and the tbo）。所有进入试验的患者都必须记录在移动性方面的障碍，该患者被定义为异常的移动措施（十英尺步行时间，360度转弯，移动技能协议得分或6分钟步行距离）以及骨吸收或构造标记，至少是正常水平的两倍。当患有paget病的患者进入研究时，他们将进行基线措施，然后随机分配以在六个小时或安慰剂中静脉注射90mg。治疗后一个，三和六个月将进行测量。移动性障碍的变化将通过测量十英尺步长时间的变化（主要响应变量），移动技能协议得分，转弯360度的步骤或步行六分钟的距离来评估。功能状态障碍的变化将通过功能状态问卷（FSQ）评估。功能状态的主要响应变量将是FSQ日常生活规模的工具活动。疼痛的变化将由西避风港疼痛库存评估。心理社会表现障碍的变化将通过Rosenberg自尊量表，Beck抑郁量表和Hopkins症状清单90进行测量。骨重塑活性的变化将在测量血清碱性磷酸酶水平以及尿羟基丙烯和N-抑菌肽排泄。结果：患者继续积极招募并参与该试验。在过去的一年中，对GCRC的26例患者进行了评估，这些患者是该研究的潜在候选者。在二十六个中，有六人入学，另外两个人获得了参加研究的机会，但尚未同意。我们已经治疗了六名pamidronate，这是第二代双膦酸盐，并显示出迁移率和功能状况障碍以及骨重塑活性的改善。意义：Paget的骨骼疾病是一种慢性骨骼疾病，影响老年人，其特征是骨骼重塑增加的区域，可能导致疼痛，畸形，继发性关节炎，骨折和很少的恶性变性。几项研究表明，paget病在60岁以上的1.8-5％和90岁年龄的人中有10％。改进的治疗将增强这些患者在正常生活活动中起作用的能力。未来的计划：自从开始试验以来，FDA已批准了两种新的双膦酸盐来治疗Paget的骨骼疾病：Alendronate（Fosamax）和Riscesronate（Actonel）。这两种药物都是口服制剂，有些患者希望接受口服药物而不是静脉注射。更重要的是，这些药物使许多患者对持续24至36个月的paget病进行生化和临床缓解。这意味着，许多患者转介评估paget病的人不需要像我们最初计划的这项研究那样频繁地治疗其疾病。